Vol 64, No 2 (2019)

REVIEWS

UNDERESTIMATED INFECTION - ON THE QUESTION OF THE HUMAN ADENOVIRUS PATHOGENICITY FACTORS

Ageeva M.R., Yatsyshina S.B.

Abstract

Human adenoviruses cause different organ infections of varying severity, from asymptomatic to severe cases with lethal outcome, that are registered everywhere. Detailed and focused study of factors predisposing to a severe course of infection is required. The literature contains information indicating the association of severe adenoviral respiratory diseases with certain types of adenovirus, primarily type 7. This review highlights the possible causes of increased pathogenicity of some types of adenovirus and their association with severe forms of infection. Pathogenicity factors include the ability of adenovirus to bind the specific cellular receptors, the formation of subviral particles, the interaction with blood proteins, in particular the coagulation factor X, as well as the features of the early genes E1A, E1B, E3, E4. In addition, the severity of the disease may be affected by the presence or absence of pre-existing antibodies specific to certain types of adenoviruses. Chronic diseases or immunosuppression also increase the risk of severe adenovirus infection. The information presented in this review may elucidate the pathogenesis of adenovirus infection, and help to develop new features for prevention and treatment.
Problems of Virology. 2019;64(2):53-62
pages 53-62 views

ORIGINAL RESEARCH

EVOLUTION OF PANDEMIC INFLUENZA VIRUS A(H1N1)PDM09 IN 2009-2016: DYNAMICS OF RECEPTOR SPECIFICITY OF THE FIRST HEMAGGLUTININ SUBUNIT (HA1)

Lvov D.K., Bogdanova V.S., Kirillov I.M., Shchelkanov M.Y., Burtseva E.I., Bovin N.V., Fedyakina I.T., Prilipov A.G., Alhovsky S.V., Samokhvalov E.I., Proshina E.S., Kirillova E.S., Syroeshkin A.V.

Abstract

Introduction. The new reassortant of the swine flu virus A(H1N1)pdm09, which emerged in 2009, overcame the species barrier and caused the 2009-2010 pandemic. One of the key points required for the influenza virus to overcome the species barrier and adapt it to humans is its specific binding to the receptors on the epithelium of the human respiratory tract.Targets and goals. Studying the dynamics of changes in receptor specificity (RS) of the HA1 subunit of the hemagglutinin of the influenza A(H1N1)pdm09 virus strains isolated during the period 2009-2016 on the territory of the Russian Federation, and an analysis of the possible impact of these changes on the incidence rates of the population of the Russian Federation of pandemic influenza in certain epidemic seasons. Material and Methods. Standard methods of collecting clinical materials, isolation of influenza viruses, their typing and genome sequencing were used. For the study of RS of influenza A virus (H1N1)pdm09, the method of solid phase sialosidenzyme analysis was used. Results. It is shown that the change in the parameter W3/6 , which characterizes the degree of a2-3 receptor specificity (a2-3-RS) of the influenza virus A(H1N1)pdm09 over a2-6-RS, coincides with the change in the incidence rates of the Russian Federation’s pandemic flu in separate epidemic seasons. There is a tendency to increase the affinity of the virus A(H1N1)pdm09 to α2-3 analogs of the sialyl-glycan receptors of the human respiratory tract epithelium - α2-3-sialoglycopolymers (α2-3-SGP), and falls to α2-6-SGP, with the virus showing the greatest affinity for sulfated sialoglycopolymers. Discussion. Screening for RS strains of influenza A (H1N1)pdm09 virus isolated on the territory of the Russian Federation in 2009-2016 revealed a decrease in the affinity of viruses for a2-6-sialosides, especially for 6’SL-SGP, which is probably due to the presence of amino acid substitutions in the 222 and 223 positions of RBS HA1 viruses. Previous studies have shown that the presence of such substitutions correlates with an increase in the virulence of the influenza A virus (H1N1)pdm09 [16, 23]. Probably, the pandemic virus has evolved towards the selection of more virulent pneumotropic variants. Conclusion. Monitoring of the receptor specificity of a pandemic influenza virus makes it possible to identify strains with altered RS to the epithelium of the human respiratory tract and an increased ability to transfer from person to person. Change in the period 2009-2016 the W3/6 parameter characterizing the degree of α2-3-RS excess of the influenza A(H1N1)pdm09 virus over α2-6-RS, coincides with the change in the incidence rates of the pandemic influenza population of the Russian Federation in certain epidemic seasons.
Problems of Virology. 2019;64(2):63-72
pages 63-72 views

CHANGE OF PHENOTYPIC PROPERTIES OF ESCAPE MUTANTS AND READAPTANTS OF INFLUENZA VIRUS A (H1N1) PDM09 UNDER THE INFLUENCE OF SELECTED MUTATIONS IN THE MOLECULE OF HEMAGGLUTININ

Timofeeva T.A., Rudneva I.A., Shilov A.A., Balanova M.A., Artemov E.K., Kushch A.A., Masalova O.V., Klimova R.R., Grebennikova T.V., Kaverin N.V.

Abstract

Introduction. After the emergence and spread of pandemic H1N1 viruses in 2009, antigenic epitopes recognized by neutralizing antibodies against the hemagglutinin of influenza A/Moscow/01/09(H1N1)pdm09 viruses were studied. Targets and goals. The purpose of the study was to obtain readapted variants of the virus from a low-virulent escape-mutant that has an increased affinity of the avian and the human types cellular receptors compared to the wild type and the comparative study of their antigenic and receptor specificity. Material and methods. Viruses were accumulated in 10-day-old chicken embryos. The MAB panel against HA of influenza virus strain A/IIV-Moscow/01/09(H1N1)sw1 was used in the form of ascites fluids from mice. Immunization of mice, HI testing, elution of viruses from chicken erythrocytes, PCR and sequencing of readapted variants were performed by standard methods. Results. The amino acid substitution A198E acquired in the process of readaptation leads to changes in the antigenic specificity. A correlation was found between a decrease in virulence of a low-virulent escape mutant associated with the substitution D190N in the hemagglutinin molecule and an increase in the hemagglutinating titer to inhibitors in normal mouse serum. Viruses with low affinity of cellular receptor analogs and carrying amino acid substitutions have an increased ability to elute from chicken erythrocytes. Discussion. The results discuss the effect of mutations in the HA molecule of the influenza A(H1N1)pdm09 virus to the change in antigen specificity; virulence for mice, adsorption-elution at cellular receptors. Conclusion. A comparative study of the antigenic specificity and receptor-binding activity of the escape mutants was conducted for the hemagglutinin of the influenza virus A/Moscow/01/2009 (H1N1)swl, and the readapted variants obtained for one of the escape mutants with reduced virulence for mouse. Monitoring the pleiotropic effect of mutations in the hemagglutinin H1 molecule is necessary to predict variants of the virus with pandemic potential.
Problems of Virology. 2019;64(2):73-78
pages 73-78 views

MOLECULAR GENETIC CHARACTERISTICS OF HIV-1 VARIANTS ISOLATED IN THE SUBJECTS OF THE RUSSIAN FAR EAST

Kotova V.O., Trotsenko O.E., Balakhontseva L.A., Bazykina E.A.

Abstract

Introduction. Molecular-genetic monitoring of human immunodeficiency virus (HIV) drug-resistant strains circulation as well as analysis of territorial peculiarities of different genetic variants prevalence of the virus is a crucial part of epidemiological surveillance over HIV-infection spread. Objective of the research - to analyze the prevalence of HIV-1 genetic variants among HIV-positive people living in different constituent entities of the Far Eastern Federal District. Material and methods. Molecular-genetic analysis of the Pol-gene that is coding protease and a part of reverse transcriptase of HIV-1 was performed for a total number of 206 blood plasma samples. The biological material was collected from HIV-positive people living in Sakhalin, Magadan and Amur regions, Jewish Autonomous District, Khabarovsk region, Republic of Sakha (Yakutia) and Chukotka Autonomous Region (constituent entities of the Russian Federation in the Russian Far East). Results. The research demonstrated that HIV-1 sub-subtype A6 continues to be dominant and comprises 72.1±3.1% of all isolated subtypes in the regions of the Russian Far East. HIV-1 subtype B was identified in 14 cases (6.8±1.8%) and subtype C in 4 cases (1.9±1.0%). Spectrum of HIV-1 recombinant forms was determined for some regions. We identified five types of HIV-1 circulating recombinant forms (CRF): CRF03_AB - 2 (0.9±0.7%), CRF02_AG - 8 (3.9±1.3%), CRF63_02A1 - 27 (13.1±2.4%), CRF11_cpx - 1 (0.5±0.5%), CRF01_AE - 3 (1.5±0.8%). High heterogeneity of the virus was registered in the Jewish Autonomous District. Discussion. The conducted research revealed genetic differences in the landscape of HIV-1 subtypes circulation as well as differences in HIV-1 recombinant forms distribution frequency in the Russian Far East. Current findings are due to expansion of migration flows that promote cross-border importation and further spread of different HIV-1 genetic variants among population of the Far Eastern Federal District. Conclusion. The conducted research revealed that the molecular-genetic monitoring of HIV-1 genovariants should involve not only regions with high HIV-abundance but also with low HIV-prevalence and incidence.
Problems of Virology. 2019;64(2):79-89
pages 79-89 views

DEVELOPMENT AND PROPERTIES OF NEUTRALIZING MONOCLONAL ANTIBODIES FOR FUSION PROTEIN OF RESPIRATORY SYNCYTIAL VIRUS

Kushch A.A., Klimova R.R., Fedorova N.E., Masalova O.V., Niconova A.A., Lesnova E.I., Momotyuk E.D., Demidova N.A., Samartseva T.G., Zverev V.V.

Abstract

Introduction. Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections in infants and the elderly. The absence of a wide range of therapeutic drugs and vaccines indicates to the high relevance of the development of new effective drugs for the prevention and treatment of RSV infections. Purpose: to obtain highly active and specific monoclonal antibodies (MAbs) capable of detecting RSV in infected cells and neutralizing the infectious activity of the virus in vitro. Material and methods. RSV reference strains of group A 2 subgroups (A2 and Long) were propagated in HEp-2 and MA-104 cell lines, respectively. Mice were immunized with purified RSV A2 virus. MAbs were obtained using hybridoma technology. Results. A panel of 6 MAbs reacting with RSV strains А2 and Long has been obtained. Four MAbs were IgG (IgG2a or IgG2b subtype), two MAbs were IgM. All MAbs reacted with RSV F-protein in immunochemical tests. The MAbs actively reacted with RSV in ELISA, in immufluorescence and peroxidase staining of infected cells, and in immunodot test. Five out of 6 MAbs neutralized of RSV in cell culture. Different properties of MAbs suggest that they target different antigenic sites of F-protein. Discussion. Comparative analysis suggests that the obtained MAbs can be used for the development of diagnostic preparations, for RSV detection in clinical materials and confirmation of infection etiology by rapid culture method. Conclusion. High activity and specificity of MAbs indicate that they can serve as a basis for development vaccines and preventive medicines.
Problems of Virology. 2019;64(2):90-96
pages 90-96 views


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